Project Summary/Abstract Oral health is associated with nutritional intake and overall well-being in elderly populations and progressively deteriorates with aging. In addition, salivary gland function, which plays a major role in oral defense, also decreases with age. However, the mechanisms involved in this age-related decline have not been comprehensively studied due to a lack of proper laboratory animal models for studying changes in oral health with aging. The common marmoset is a relatively short-lived non-human primate (NHP) that recapitulates many of the physiological changes that occur in human aging. At the University of Texas Health Science Center at San Antonio (UTHSCSA), we maintain a cohort of aging marmosets for a study testing whether the anti-aging drug rapamycin, an inhibitor of mTOR signaling, can extend longevity and delay markers of physiological aging in this species. This multiple PI proposal will use this existing cohort of marmosets to establish an aging NHP model for studying oral health and salivary gland function and determine whether oral health in aging can be preserved by an anti-aging intervention. Specific Aim (1): Establish the changes in oral health and relationship to general physiological function in aging marmosets and test whether inhibition of mTOR improves these outcomes. We will document prevalence of caries, periodontal health indices, oral mucosa lesions of young and old animals and analyze the microbiome of subgingival plaques and cytokine profiles of gingival crevicular fluid. The outcomes from this cohort of animals will be used to compare changes in oral health with changes in general physiological health and immunological function during aging already being collected in this cohort. All outcomes will also be measured in rapamycin-treated old marmosets to evaluate the role of mTOR in oral health and age- associated periodontal bone loss. Specific Aim (2) Establish changes in salivary gland function with age in the marmoset and determine whether mTOR inhibition delays these salivary gland outcomes. Whole saliva from young and old marmosets will be collected to measure salivary flow rate, major antimicrobial proteins, salivary cytokine profiles, and the microbiome and document changes in salivary innate and adaptive immunity during aging. Age-related salivary structural changes will be evaluated by histological analysis of specimens from cadavers and needle biopsies and live animal imaging. The effect of rapamycin on salivary gland function/structure will be assessed and correlation of salivary gland function and general/oral health will also be determined. Significance and Innovation: The proposed exploratory study combines expertise from the fields of aging and geriatric dentistry to develop a novel NHP model for studying changes in oral health with aging and linking these changes to general physiological/immunological decline with aging. The successful establishment of this model, and the effect of an anti-aging intervention, will drive novel pre-clinical intervention trials for oral and other geriatric diseases.